Abstract
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is an inflammatory cytokine that modulates several biological responses by inducing chemokines and proinflammatory cytokines. We hypothesized that TWEAK could promote secretion of IL-17, an amplifier of inflammatory arthritis. To test this, we investigated the capacity of TWEAK to induce IL-17 production in T cells via the fibroblast growth factor-inducible gene 14 (Fn14, also known as TWEAK receptor) signal pathway in rheumatoid arthritis (RA). Fn14 and IL-17 were highly expressed in arthritic tissues of collagen-induced arthritis (CIA) mice. TWEAK induced production of IL-17 alone and synergistically with lipopolysaccharide. In naïve murine T cells, TWEAK promoted Th17 differentiation. The expression of Fn14 was predominant in Th17 cells. TWEAK and IL-17 concentrations were significantly higher in synovial fluid and serum in RA patients than OA patients. In addition, we identified CD4+IL-17+Fn14+ cells in synovium from RA patients. TWEAK promoted IL-17 production synergistically with IL-23 or IL-21 and blockade of Fn14 with Fn14-Fc suppressed Th17 differentiation. Conversely, this treatment enhanced Treg differentiation. These results suggest that TWEAK induces IL-17 production and may be a therapeutic target in the treatment of RA.
Original language | English (US) |
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Pages (from-to) | 143-149 |
Number of pages | 7 |
Journal | Cytokine |
Volume | 60 |
Issue number | 1 |
DOIs | |
State | Published - Oct 2012 |
Externally published | Yes |
Keywords
- Fibroblast growth factor inducible gene 14 (Fn14)
- Interleukin-17
- Rheumatoid arthritis
- Th17
- Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Biochemistry
- Molecular Biology
- Hematology